Interaction of insulin with its receptor. I. Possible role of a histidine-arginine interaction

The interaction of beef and pork insulin with its receptors on rat liver plasma membranes has been studied as a function of pH in tris buffer. The dissociation binding constant decreased from 6.5 to 1.2 nM as the pH was increased from 6.8 to 7.8. Analysis indicated that this was the result of the deprotonation of a single residue with a pK'A of 7.62 at 20 degrees C. The enthalpy change associated with this deprotonation was estimated to be -7,500 cal/mol. On the basis of these parameters it is suggested that this group is a histidine residue on the surface of the insulin receptor. The positively charged group on the insulin molecule which interacts with this histidine was not either of the N-terminal residues, nor the lysine at position B-29; by elimination, it appears to be the B-22 arginine residue.